Perinatal exposures may lead to increased risk of childhood cancers, as well as those later in life. Preconception parental, transplacental, and/or neonatal exposures may be involved. Studies with animal models are utilized to increase understanding of underlying cellular and molecular mechanisms.Recently we demonstrated that the anti-AIDS drug AZT, currently prescribed as the standard of care for HIV-positive pregnant women, is a perinatal carcinogen in mice, causing an increase in tumor incidence in multiple tissues of the offspring. The mechanism of this effect is of interest, as this knowledge could assist in understanding and managing human risk. One possibility is that AZT could cause oxidative DNA damage; it is known to damage mitochondria. We have assayed for an increase in oxidative DNA damage, as indicated by the pro-mutagenic lesion 8-oxo-dG, in the fetal tissue of mice and patas monkeys exposed to AZT transplacentally. At the carcinogenic dose of AZT given to pregnant mice, there was a significant increase in 8- oxo-dG in livers and kidneys of the fetuses. More limited data from the monkeys suggested that such an increase could occur in primate fetuses also. Studies of mitochondrial damage as an important target for cancer-related fetal toxicity are in progress.AIDS Title: Transplacental causation of oxidative DNA damage by AZT. - 8-Oxo-dG, AZT, fetus, liver, kidney, reactive oxygen, perinatal, Transplacental carcinogenesis, - Neither Human Subjects nor Human Tissues